Lomustine Combined With Anlotinib as Interventional Therapy for Extensive-stage Small Cell Lung Cancer Resistant to Second-line and Above Treatment (Aurora003)

A Single-arm, Phase II Interventional Study to Evaluate the Efficacy and Safety of Lomustine Combined With Anlotinib in Patients With Extensive-stage Small Cell Lung Cancer Resistant to Second-line and Further Lines of Treatment

This single-arm phase II study aims to evaluate the efficacy and safety of lomustine combined with anlotinib in patients with extensive-stage small cell lung cancer resistant to second-line and above systemic treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: SCLC, Extensive Stage
• Intervention / Treatment: Drug: Lomustine; Drug: Anlotinib

Detailed Description

This is a single-arm phase II clinical study evaluating the efficacy and safety of lomustine combined with anlotinib in extensive-stage small cell lung cancer resistant to second-line and subsequent treatments. A total of 46 patients with extensive-stage small cell lung cancer who have received at least two lines of prior systemic therapy will be enrolled and treated with lomustine plus anlotinib. The primary endpoint is investigator-assessed objective response rate (ORR). Secondary endpoints include investigator-assessed progression-free survival (PFS), investigator-assessed disease control rate (DCR), intracranial response rate assessed per RANO criteria (RANO-IRR), investigator-assessed overall survival (OS), adverse events, quality of life (QOL) scores and safety profiles.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1: Aged 18-75 years, without gender restriction.

  2: Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC), classified as extensive-stage disease according to the Veterans Administration Lung Study Group (VALSG) staging system.

  3: Has received at least two lines of prior systemic antitumor therapy.

  4: Has at least one measurable lesion as defined by RECIST 1.1 criteria.

  5: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

  6: Adequate organ function meeting the following criteria: Hematological function: Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 100×10⁹/L; hemoglobin (Hb) ≥ 90 g/L. Hepatic and renal function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×ULN (≤ 5×ULN for patients with liver metastases); serum creatinine (Cr) ≤ 1.5×ULN; estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m². Coagulation function: International normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

  7: Expected survival time ≥ 3 months.

  8: Voluntarily signs the informed consent form and is willing and able to comply with the study protocol and follow-up requirements.

Exclusion Criteria:

• 1: Previous treatment with lomustine, anlotinib, or other similar anti-angiogenic TKIs.

  2: Uncontrolled central nervous system (CNS) metastases (e.g., unstable or symptomatic brain metastases, or those requiring ongoing glucocorticoid therapy).

  3: Active bleeding or high bleeding risk (e.g., history of massive gastrointestinal hemorrhage or cerebral hemorrhage within the past 6 months, or presence of unhealed wounds or ulcers).

  4: Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) or severe cardiovascular diseases (e.g., myocardial infarction, severe arrhythmia, heart failure within the past 6 months).

  5: Active infection (such as pneumonia, sepsis) or uncontrolled systemic diseases (such as uncontrolled diabetes, autoimmune diseases).

  6: Pregnant or lactating females. Female participants must use effective contraception during treatment and for 6 months after the last dose of study treatment; male participants must use effective contraception during treatment and for 3 months after the last dose of study treatment.

  7: History of other malignant tumors within the past 5 years, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and other cured malignancies.

  8: Known hypersensitivity to lomustine, anlotinib, or any excipient in their formulations.

  9: Any other condition deemed inappropriate for participation in this study by the investigator (e.g., mental disorders, inability to comply with follow-up procedures).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lomustine combined with anlotinib; Oral lomustine 60 mg/m² once daily on day 1 every 6 weeks, combined with oral anlotinib. The initial dose of anlotinib is determined by the investigator, with optional doses of 12 mg, 10 mg or 8 mg once daily on days 1 to 14 every 3 weeks.	Drug: Lomustine; Oral lomustine 60 mg/m² once daily on day 1, every 6 weeks; Drug: Anlotinib; Oral administration, initial dose 12 mg, 10 mg or 8 mg once daily on days 1-14 of every 3-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Investigator-assessed ORR per RECIST 1.1 in ES-SCLC patients treated with Lomustine combined with anlotinib	Baseline at screening, after every 2 treatment cycles (each cycle is 21 days), end of treatment, up to disease progression, assessed up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event (AE)	Record all new or worsening unfavorable medical events, grade and calculate incidence according to CTCAE 5.0	From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months
Disease Control Rate (DCR)	According to RECIST 1.1, proportion of subjects achieving CR, PR, or stable disease (SD) in total enrolled population	Time Frame: Baseline and after every 2 treatment cycles (each cycle is 21 days), up to disease progression, death, or study withdrawal, whichever occurs first，assessed up to approximately 24 months
progression free survival	Time from first treatment to disease progression or death from any cause, whichever occurs first	Date of first study treatment to date of disease progression or death from any cause, last follow-up, assessed up to approximately 24 months
Quality of Life Score（QOL Score）	The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was adopted for patient self-assessment. The scale consists of 30 items, including 5 functional scales, 9 symptom scales and 1 global health status / quality of life scale. Each item is scored on a 1-4 Likert scale, and all scale scores are standardized to a range of 0-100. Higher scores in functional and global quality of life scales and lower scores in symptom scales indicate better quality of life and health status of patients.	At baseline, every 6 weeks during treatment until disease progression or death，assessed up to approximately 24 months

Collaborators and Investigators

• Sponsor: Yayi He

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Amides; Nitrosourea Compounds; Urea; Nitroso Compounds; Lomustine; anlotinib
• Other Study ID Numbers: 2026LY0102; MR-31-26-032631 (Other Identifier: National Medical Research Registration and Filing System)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No